The “Dialogue” Between Central and Peripheral Immunity After Ischemic Stroke: Focus on Spleen

Abstract

The immune response generated by the body after the incidence of ischemic stroke, runs through the comprehensive process of aftermath. During this process of ischemic stroke, the central neuroinflammation and peripheral immune response seriously affect the prognosis of patients, which has been the focus of research in recent years. As this research scenario progressed, the “dialogue” between central nervous inflammation and peripheral immune response after ischemic stroke has become more closely related. It’s worth noting that the spleen, as an important peripheral immune organ, plays a pivotal role in this dialogue. Multiple mechanisms have previously been reported for brain-spleen crosstalk after ischemic stroke. Further, neuroinflammation in the brain can affect the peripheral immune state by activating/inhibiting spleen function. However, the activation of the peripheral immune inflammatory response can work reversibly in the spleen. It further affects intracerebral neuroinflammation through the injured blood-brain barrier. Therefore, paying close attention to the role of spleen as the pivot between central and peripheral immunity in ischemic stroke may help to provide a new target for immune intervention in the treatment of ischemic stroke. In the present review, we reviewed the important role of spleen in central neuroinflammation and peripheral immune response after ischemic stroke. We summarized the relevant studies and reports on spleen as the target of immune intervention which can provide new ideas for the clinical treatment of ischemic stroke.

The potential risk factors of early-onset post-stroke depression from immuno-inflammatory perspective

“…The data, however, showed here that there was no association between SV and PSD status, but lower SA was significantly associated with PSD status in the presence of CRP rs2794520 C/T genotype and rs1205 C/T genotype. The mechanisms underlying the associations may be that owing to the contribution of CRP polymorphism and CRP levels to immuno-inflammatory process ( 32 , 37 ), patients with the C/T genotypes of rs2794520 and rs1205 may be in a more active inflammatory state so that immune cells and cytokines produced abundantly in the spleen, in response to brain vascular damage, were released into the bloodstream and migrated to the site of brain insult ( 17 , 20 ), aggravating secondary brain inflammatory response which influences serotonin metabolism and causes noradrenergic system and HPA axis imbalance, may culminate in PSD ( 6 , 42 ). There in addition were evidence from animal studies for the involvement of pro- and anti-inflammatory cytokines produced by splenic cells in the formation of depression like behavior ( 43 , 44 ).…”

“…It is believed that activation of peripheral immunity and secondary intracerebral neuroinflammation after stroke are mainly the result of brain-spleen communication (16)(17)(18). The spleen is a major lymph organ containing an abundance of immunological cells, which can rapidly deploy the distribution of immune cells in the system to fight injury including brain insult (19).…”

Low Lymphocyte-to-Monocyte Ratio as a Possible Predictor of an Unfavourable Clinical Outcome in Patients with Acute Ischemic Stroke after Mechanical Thrombectomy

“…The number of peripheral lymphocytes decreases exponentially for up to seven days following AIS, with the lowest level occurring after 12 hours [ 8 ]. This dramatic decrease is caused by activation of the hypothalamus-pituitary axis and sympathetic nervous system [ 34 ]. Although the specific molecular mechanism has yet to be elucidated, studies have indicated that one of the DAMPs, HMGB-1, plays an important role during the process of immunosuppression following AIS.…”

Advancement of epigenetics in stroke

“…Unlike DNA methylation, histone modification exclusively occurs at the amino-terminal tail protruding out of the histone subunit and is a short-term reversible modification. The amino-terminal tails are subjected to post-translational modification namely methylation, acetylation, phosphorylation, and ubiquitination ( Yu et al, 2021 ). Post-translational modification of amino-terminal tails is associated with DNA repair, activation or repression of gene expression, telomere integrity, and the total interaction changes in response to these modifications are determined by “histone code” ( Ng et al, 2018 ).…”